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ORIGINAL RESEARCH ARTICLE

Cancer-testis antigens in gastric adenocarcinoma: Integration of differential expression, clinical associations, survival, and co-expression networks

Jade Dias Valente1 ,  Livia Érika Carlos Marques1* ,  Ronald Matheus da Silva Mourão1 ,  Bianca de Fátima dos Reis Rodrigues1 ,  Louise Sousa de Souza1 ,  Jéssica Manoelli Costa da Silva1 ,  Samir Mansour Moraes Casseb1 ,  André Salim Khayat1 ,  Samia Demachki1 ,  Geraldo Ishak1 ,  Fabiano Cordeiro Moreira1 ,  Rommel Mario Rodríguez Burbano2 ,  Paulo Pimentel de Assumpção1
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1 Oncology Research Center, Federal University of Pará, Belém, Pará, Brazil
2 Molecular Biology Laboratory, Ophir Loyola Hospital, Belém, Pará, Brazil
MI, 025510135 https://doi.org/10.36922/MI025510135
Received: 16 December 2025 | Revised: 12 March 2026 | Accepted: 17 March 2026 | Published online: 24 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Gastric adenocarcinoma (GAC) remains one of the deadliest malignancies worldwide, and the identification of molecular biomarkers is essential to improve prognostic stratification and guide therapeutic strategies. Cancer-testis antigens (CTAs) represent promising targets for immunotherapy, yet their expression landscape in GAC remains limited, especially when considering comprehensive and updated gene lists. In this study, we analyzed 389 samples, including tumor, peritumoral, metaplastic, and normal tissues, using RNA sequencing data to characterize the transcriptional profile of CTAs in GAC. We identified 104 CTAs differentially expressed among groups, with a predominance of upregulated genes in tumors compared with other tissues. The expression of several CTAs, such as MAGEA2, MAGEA3, MAGEA6, MAGEA12, CTCFL, IGF2BP1, and GAST, showed significant associations with clinically relevant variables, including tumor–node–metastasis staging, lymph node involvement, metastasis, histological subtype, and therapeutic management. Survival analysis revealed 17 CTA genes associated with overall survival, of which 14 correlated with poor prognosis, whereas PIK3R3, SYCE1L, and ZNF683 demonstrated a protective effect. Co-expression analysis identified five well-defined functional modules, reflecting coordinated CTA signatures related to germline reprogramming, proliferation, and immune remodeling within the tumor microenvironment. Collectively, our results provide the most comprehensive characterization of CTAs in GAC to date, highlighting genes with clinical relevance, prognostic value, and translational potential as candidates for future personalized immunotherapeutic approaches.

Keywords
Antigens
Cancer-testis antigens
Gastric cancer
Molecular biomarkers
Therapeutic targets
Transcriptomics
Funding
This research was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (Funding Code 001), and by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (385189/2025-7), through the awarding of scholarships.
Conflict of interest
The authors declare that this research was conducted without any commercial or financial relationships that could be interpreted as potential conflicts of interest.
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